Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer’s disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1—a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT—on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer’s disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.

Sleep is a conserved behavioral state. Invertebrates typically show quiet sleep, whereas in mammals, sleep consists of periods of non-rapid-eye-movement sleep (NREMS) and REM sleep (REMS). We previously found that the transcription factor AP-2 promotes sleep in C. elegans and Drosophila. In mammals, several paralogous AP-2 transcription factors exist. Sleep-controlling genes are often conserved. However, little is known about how sleep genes evolved from controlling simpler types of sleep to govern complex mammalian sleep. Here, we studied the roles of Tfap2a and Tfap2b in sleep control in mice. Consistent with our results from C. elegans and Drosophila, the AP-2 transcription factors Tfap2a and Tfap2b also control sleep in mice. Surprisingly, however, the two AP-2 paralogs play contrary roles in sleep control. Tfap2a reduction of function causes stronger delta and theta power in both baseline and homeostasis analysis, thus indicating increased sleep quality, but did not affect sleep quantity. By contrast, Tfap2b reduction of function decreased NREM sleep time specifically during the dark phase, reduced NREMS and REMS power, and caused a weaker response to sleep deprivation. Consistent with the observed signatures of decreased sleep quality, stress resistance and memory were impaired in Tfap2b mutant animals. Also, the circadian period was slightly shortened. Taken together, AP-2 transcription factors control sleep behavior also in mice, but the role of the AP-2 genes functionally diversified to allow for a bidirectional control of sleep quality. Divergence of AP-2 transcription factors might perhaps have supported the evolution of more complex types of sleep.

BackgroundDelirium and dementia are prominent psychiatric diseases in old age and connected with poor outcomes for people affected. Nevertheless, there is a lack of knowledge concerning the long-term prognosis of patients with dementia and delirium. This study analyzes mortality, readmission rates and discharge destinations of patients with dementia or delirium superimposed on dementia (DSD) within 3 years after discharge from hospital.MethodsA cross-sectional, monocentric cohort study was conducted at the department of geriatric psychiatry of the LVR hospital cologne, using structured telephone interviews and analyses from the clinical information system. All patients with dementia and DSD, admitted between December 2014 and November 2015, were screened for eligibility.ResultsIn total, 113 patients were included, 49 patients with dementia (M 80 years, female 49%) and 64 with DSD (M 82 years, female 47%). Three years after discharge, 66 patients (58%) had died (95% CI 91.9–112.5; p = 0.53). Within the first 3 months, 9 patients (14%) with DSD deceased, but no patient from the dementia group (95% CI 11.3–12.7; p = 0.01). Out of all patients, 17 patients were readmitted and nursing homes were the predominant discharge destination (55%).ConclusionsThis analysis revealed a high post-discharge mortality rate of patients with dementia and DSD. For patients with DSD, a close clinical monitoring, mainly within the first 3 months after discharge, should challenge the significantly increased acute-mortality. These findings should set the pattern for a comprehensive analysis of long-term effects of dementia and DSD. More studies are required for better understanding and comparability in this field of research and healthcare.

Objectives Dance as a non-pharmacological therapy is commonly used in dementia care, although the evidence of its effects remains unclear. This study systematically reviewed the effects of dance interventions on neuropsychiatric symptoms (NPS) in people living with dementia. To systematically identify and evaluate dance interventions, a standardized terminology for Dance-Specific Activity (DSA) is proposed. Methods Literature search was conducted on electronic databases until April 30th 2021. Studies were included when they quantified the effects of DSA on NPS in people with clinical diagnosis of dementia. Included studies were analyzed in detail for NPS. Study quality was assessed by PEDro scale (German version). Results 4 studies were included. The studies differed in study design, intervention protocols, dance styles, or measurement tools, and were generally of low study quality. Two trials showed improvements in NPS and 2 trials showed no exacerbation of NPS after DSA. Conclusions The results of the 4 available trials indicate a positive tendency towards the effects of DSA, but considering the limitations of the few available studies, a clear statement about the effects of DSA is not possible yet. Based on the included trials, the following implications for clinical research and routine care can be derived: (1) DSA seems to be a practical terminology for identifying dance interventions (2) DSA seems to be a safe intervention for people living with dementia. (3) Different dance styles can be used. (4) DSA approaches should be better structured by differentiating between the domains type, content, intention, and protocol of the intervention.

Nimodipine prevents cerebral vasospasm and improves functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). The beneficial effect is limited by low oral bioavailability of nimodipine, which resulted in an increasing use of nanocarriers with sustained intrathecal drug release in order to overcome this limitation. However, this approach facilitates only a continuous and not an on-demand nimodipine release during the peak time of vasospasm development. In this study, we aimed to assess the concept of controlled drug release from nimodipine-loaded copolymers by ultrasound application in the chicken chorioallantoic membrane (CAM) model. Nimodipine-loaded copolymers were produced with the direct dissolution method. Vasospasm of the CAM vessels was induced by means of ultrasound (Physiomed, continuous wave, 3 MHz, 1.0 W/cm2). The ultrasound-mediated nimodipine release (Physiomed, continuous wave, 1 MHz, 1.7 W/cm2) and its effect on the CAM vessels were evaluated. Measurements of vessel diameter before and after ultrasound-induced nimodipine release were performed using ImageJ. The CAM model could be successfully carried out in all 25 eggs. After vasospasm induction and before drug release, the mean vessel diameter was at 57% (range 44–61%) compared to the baseline diameter (set at 100%). After ultrasound-induced drug release, the mean vessel diameter of spastic vessels increased again to 89% (range 83–91%) of their baseline diameter, which was significant (p = 0.0002). We were able to provide a proof of concept for in vivo vasospasm induction by ultrasound application in the CAM model and subsequent resolution by ultrasound-mediated nimodipine release from nanocarriers. This concept merits further evaluation in a rat SAH model. Graphical abstract